Assessment of Immunogenicity and Efficacy of CV0501 mRNA-Based Omicron COVID-19 Vaccination in Small Animal Models
Abstract
:1. Introduction
2. Methods and Materials
2.1. Vaccines
2.2. Animal Models
2.3. Dose Response and Booster Studies
2.4. Neutralizing Antibody Titers
2.5. Enzyme-Linked Immunosorbent Spot (ELISpot) Assay
2.6. ACE2 Binding Inhibition Assay Methodology
2.7. Hamster Challenge Model
2.7.1. Immunizations
2.7.2. Challenge Infection
2.7.3. Viral RNA Detection and Quantification
2.7.4. Surrogate ELISA
2.7.5. Neutralizing Antibody Titers
2.7.6. Statistical Analysis
3. Results
3.1. CV0501 Induces nAb Responses against SARS-CoV-2 Variants in Wistar Rats
3.2. CV0501 Boosting Induces Cross-nAbs against SARS-CoV-2 Variants in Ancestral-Primed Wistar Rats
3.3. CV0501 Protects against Weight Loss and Viral Replication in the Respiratory Tract in Syrian Hamsters
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Name | Encoded SARS-CoV-2 Variant | mRNA Modification | AA Mutations in the Spike Protein * (Compared with Ancestral) | AA Mutations Specific to the RBD Region (Compared with Ancestral) |
---|---|---|---|---|
CV0501 | BA.1 (12 RBD mutations) | N1mΨ | A67V, del69–70, T95I, G142D, del143–145, del211, L212I, ins214EPE, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K and L981F. | G339D, S371L, S373P, S375F, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H |
BA.1 nonclinical | BA.1 (15 RBD mutations) | N1mΨ | A67V, del69–70, T95I, G142D, del143–145, del211, L212I, ins214EPE, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K and L981F. | As above but with 3 additional mutations: K417N, N440K and G446S |
Ancestral | Ancestral | N1mΨ | - | - |
Group | 1st Prime (Day 0) 2nd Prime (Day 21) | 1st Boost (Day 105) 2nd Boost (Day 189) | Dose Concentration | Median nAb Titers | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 21 | Day 42 | Fold-Increase Days 21–42 | Day 105 | Day 133 | Fold-Increase Days 105–133 | Day 189 | Day 217 | Fold-Increase Days 189–217 | ||||
1 | Ancestral N1mΨ | CV0501 | 2 µg | 8 | 273 | 36 | 137 | 773 | 5.6 | 386 | 2450 | 6.3 |
8 µg | 34 | 2560 | 75 | 1810 | 2185 | 1.2 | 1810 | 5430 | 3.0 | |||
2 | Ancestral N1mΨ | CV0501/ ancestral N1mΨ | 2 µg | 12 | 1093 | 91 | 480 | 905 | 1.9 | 546 | 1545 | 2.8 |
8 µg | 113 | 7241 | 64 | 1920 | 3090 | 1.6 | 1545 | 6180 | 4.0 | |||
3 | Ancestral N1mΨ | Ancestral N1mΨ | 2 µg | 5 | 170 | 34 | 160 | 240 | 1.5 | 160 | 453 | 2.8 |
8 µg | 24 | 1810 | 75 | 960 | 1358 | 1.4 | 1092 | 2185 | 2.0 | |||
4 | BA.1 nonclinical | CV0501 | 2 µg | 773 | 7241 | 9 | 4370 | 5120 | 1.2 | 3620 | 8740 | 2.4 |
8 µg | 1280 | 12,361 | 10 | 4370 | 10,240 | 2.3 | 5120 | 17,481 | 3.4 |
Median nAb Titers vs. SARS-CoV-2 Variants on Day 217 | |||||||||
---|---|---|---|---|---|---|---|---|---|
Group | 1st Prime (Day 0) 2nd Prime (Day 21) | 1st Boost (Day 105) | 2nd Boost (Day 189) | Dose Concentration | Ancestral | Delta | BA.1 | BA.2 | BA.5 |
1 | Ancestral N1mΨ | Ancestral N1mΨ | Ancestral N1mΨ | 2 µg | 3620 | 5120 | 452 | 1810 | 1280 |
8 µg | 8740 | 7241 | 2185 | 5120 | 1545 | ||||
2 | Ancestral N1mΨ | CV0501 | CV0501 | 2 µg | 1093 | 2560 | 2450 | 4370 | 1093 |
8 µg | 4370 | 8740 | 5431 | 10,240 | 5431 | ||||
3 | Ancestral N1mΨ | Bivalent CV0501/ancestral N1mΨ | Bivalent CV0501/ancestral N1mΨ | 2 µg | 7241 | 5120 | 1545 | 6180 | 1810 |
8 µg | 10,240 | 12,361 | 6180 | 12,361 | 5120 | ||||
4 | BA.1 nonclinical | CV0501 | CV0501 | 2 µg | 226 | 546 | 8740.4 | 7241 | 1280 |
8 µg | 960 | 3090 | 17,480.75 | 14,482 | 5120 |
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Roth, N.; Gergen, J.; Kovacikova, K.; Mueller, S.O.; Ulrich, L.; Schön, J.; Halwe, N.J.; Fricke, C.; Corleis, B.; Dorhoi, A.; et al. Assessment of Immunogenicity and Efficacy of CV0501 mRNA-Based Omicron COVID-19 Vaccination in Small Animal Models. Vaccines 2023, 11, 318. https://doi.org/10.3390/vaccines11020318
Roth N, Gergen J, Kovacikova K, Mueller SO, Ulrich L, Schön J, Halwe NJ, Fricke C, Corleis B, Dorhoi A, et al. Assessment of Immunogenicity and Efficacy of CV0501 mRNA-Based Omicron COVID-19 Vaccination in Small Animal Models. Vaccines. 2023; 11(2):318. https://doi.org/10.3390/vaccines11020318
Chicago/Turabian StyleRoth, Nicole, Janina Gergen, Kristina Kovacikova, Stefan O. Mueller, Lorenz Ulrich, Jacob Schön, Nico Joel Halwe, Charlie Fricke, Björn Corleis, Anca Dorhoi, and et al. 2023. "Assessment of Immunogenicity and Efficacy of CV0501 mRNA-Based Omicron COVID-19 Vaccination in Small Animal Models" Vaccines 11, no. 2: 318. https://doi.org/10.3390/vaccines11020318
APA StyleRoth, N., Gergen, J., Kovacikova, K., Mueller, S. O., Ulrich, L., Schön, J., Halwe, N. J., Fricke, C., Corleis, B., Dorhoi, A., Hoffmann, D., Beer, M., Maione, D., Petsch, B., & Rauch, S. (2023). Assessment of Immunogenicity and Efficacy of CV0501 mRNA-Based Omicron COVID-19 Vaccination in Small Animal Models. Vaccines, 11(2), 318. https://doi.org/10.3390/vaccines11020318